{"title":"一项非劣效性的III期试验，吉西他滨加卡培他滨与吉西他滨加卡铂作为一线治疗，肿瘤浸润淋巴细胞作为晚期三阴性乳腺癌患者的预后生物标志物。","authors":"Xiaodong Liu, Weipeng Zhao, Yongsheng Jia, Yehui Shi, Xu Wang, Shufen Li, Pin Zhang, Chen Wang, Chunfang Hao, Zhongsheng Tong","doi":"10.1177/17588359241240304","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Gemcitabine plus capecitabine (GX) shows survival benefit and manageable safety in patients with advanced triple-negative breast cancer (TNBC) but there is a paucity of phase III trial evidence. We aimed to compare the efficacy and safety of GX with gemcitabine plus carboplatin (GC) as first-line treatment for patients with advanced TNBC and validate the prognostic value of tumor-infiltrating lymphocytes (TILs).</p><p><strong>Methods: </strong>Patients with advanced TNBC were randomly assigned 1:1 to receive gemcitabine (1000 mg/m<sup>2</sup>) on days 1 and 8 plus oral capecitabine (1000 mg/m<sup>2</sup> twice a day) on days 1-14, or gemcitabine (1000 mg/m<sup>2</sup>) on days 1 and 8 plus carboplatin area under curve 2 on days 1 and 8. The primary endpoint was progression-free survival (PFS). TILs were analyzed by immunohistochemistry. The margin used to establish non-inferiority was 1.2.</p><p><strong>Results: </strong>In all, 187 patients were randomly assigned, with 93 in GX and 94 in GC. Median PFS was 6.1 months in the GX arm compared with 6.3 months in the GC arm. The hazard ratio for PFS was 1.148, and a 95% CI was 0.856-1.539, exceeding the non-inferiority margin of 1.2. The median overall survival (OS) was 21.0 months in the GX arm compared with 21.5 months in the GC arm. The safety profile for the GX regimen was superior to the GC regimen, especially regarding hematological toxicity. Patients with high CD8<sup>+</sup> TILs had significantly longer PFS and OS compared with patients with low CD8<sup>+</sup> TILs. In the high CD8<sup>+</sup> TIL group, the GC arm had prolonged PFS and OS compared with the GX arm.</p><p><strong>Conclusion: </strong>The trial did not meet the prespecified criteria for the primary endpoint of PFS in patients with advanced TNBC. Moreover, the GC regimen showed better efficacy compared with the GX regimen in patients with high CD8<sup>+</sup> TILs. However, the GX regimen should be considered in patients who cannot tolerate hematological toxicity.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT02207335.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241240304"},"PeriodicalIF":4.3000,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11615979/pdf/","citationCount":"0","resultStr":"{\"title\":\"A non-inferiority, phase III trial of gemcitabine plus capecitabine <i>versus</i> gemcitabine plus carboplatin as first-line therapy and tumor-infiltrating lymphocytes as a prognostic biomarker in patients with advanced triple-negative breast cancer.\",\"authors\":\"Xiaodong Liu, Weipeng Zhao, Yongsheng Jia, Yehui Shi, Xu Wang, Shufen Li, Pin Zhang, Chen Wang, Chunfang Hao, Zhongsheng Tong\",\"doi\":\"10.1177/17588359241240304\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Gemcitabine plus capecitabine (GX) shows survival benefit and manageable safety in patients with advanced triple-negative breast cancer (TNBC) but there is a paucity of phase III trial evidence. We aimed to compare the efficacy and safety of GX with gemcitabine plus carboplatin (GC) as first-line treatment for patients with advanced TNBC and validate the prognostic value of tumor-infiltrating lymphocytes (TILs).</p><p><strong>Methods: </strong>Patients with advanced TNBC were randomly assigned 1:1 to receive gemcitabine (1000 mg/m<sup>2</sup>) on days 1 and 8 plus oral capecitabine (1000 mg/m<sup>2</sup> twice a day) on days 1-14, or gemcitabine (1000 mg/m<sup>2</sup>) on days 1 and 8 plus carboplatin area under curve 2 on days 1 and 8. The primary endpoint was progression-free survival (PFS). TILs were analyzed by immunohistochemistry. The margin used to establish non-inferiority was 1.2.</p><p><strong>Results: </strong>In all, 187 patients were randomly assigned, with 93 in GX and 94 in GC. Median PFS was 6.1 months in the GX arm compared with 6.3 months in the GC arm. The hazard ratio for PFS was 1.148, and a 95% CI was 0.856-1.539, exceeding the non-inferiority margin of 1.2. The median overall survival (OS) was 21.0 months in the GX arm compared with 21.5 months in the GC arm. The safety profile for the GX regimen was superior to the GC regimen, especially regarding hematological toxicity. Patients with high CD8<sup>+</sup> TILs had significantly longer PFS and OS compared with patients with low CD8<sup>+</sup> TILs. In the high CD8<sup>+</sup> TIL group, the GC arm had prolonged PFS and OS compared with the GX arm.</p><p><strong>Conclusion: </strong>The trial did not meet the prespecified criteria for the primary endpoint of PFS in patients with advanced TNBC. Moreover, the GC regimen showed better efficacy compared with the GX regimen in patients with high CD8<sup>+</sup> TILs. However, the GX regimen should be considered in patients who cannot tolerate hematological toxicity.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT02207335.</p>\",\"PeriodicalId\":23053,\"journal\":{\"name\":\"Therapeutic Advances in Medical Oncology\",\"volume\":\"16 \",\"pages\":\"17588359241240304\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-12-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11615979/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Medical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17588359241240304\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17588359241240304","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
A non-inferiority, phase III trial of gemcitabine plus capecitabine versus gemcitabine plus carboplatin as first-line therapy and tumor-infiltrating lymphocytes as a prognostic biomarker in patients with advanced triple-negative breast cancer.
Background: Gemcitabine plus capecitabine (GX) shows survival benefit and manageable safety in patients with advanced triple-negative breast cancer (TNBC) but there is a paucity of phase III trial evidence. We aimed to compare the efficacy and safety of GX with gemcitabine plus carboplatin (GC) as first-line treatment for patients with advanced TNBC and validate the prognostic value of tumor-infiltrating lymphocytes (TILs).
Methods: Patients with advanced TNBC were randomly assigned 1:1 to receive gemcitabine (1000 mg/m2) on days 1 and 8 plus oral capecitabine (1000 mg/m2 twice a day) on days 1-14, or gemcitabine (1000 mg/m2) on days 1 and 8 plus carboplatin area under curve 2 on days 1 and 8. The primary endpoint was progression-free survival (PFS). TILs were analyzed by immunohistochemistry. The margin used to establish non-inferiority was 1.2.
Results: In all, 187 patients were randomly assigned, with 93 in GX and 94 in GC. Median PFS was 6.1 months in the GX arm compared with 6.3 months in the GC arm. The hazard ratio for PFS was 1.148, and a 95% CI was 0.856-1.539, exceeding the non-inferiority margin of 1.2. The median overall survival (OS) was 21.0 months in the GX arm compared with 21.5 months in the GC arm. The safety profile for the GX regimen was superior to the GC regimen, especially regarding hematological toxicity. Patients with high CD8+ TILs had significantly longer PFS and OS compared with patients with low CD8+ TILs. In the high CD8+ TIL group, the GC arm had prolonged PFS and OS compared with the GX arm.
Conclusion: The trial did not meet the prespecified criteria for the primary endpoint of PFS in patients with advanced TNBC. Moreover, the GC regimen showed better efficacy compared with the GX regimen in patients with high CD8+ TILs. However, the GX regimen should be considered in patients who cannot tolerate hematological toxicity.
期刊介绍：
Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).
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